Over 50 million Americans are affected by Osteoarthritis (OA), which leads to a compromised quality of life and places an enormous burden on the healthcare system. Current clinically available treatment methods mainly offer symptomatic relief but are unable to alter its natural course. Since there is no cure for the disease, early detection and appropriate therapeutic intervention potentially may stop the disease progression. Current diagnostic methods include radiography, arthroscopy and magnetic resonance imaging (MRI). Radiography can only detect gross tissue losses and hence useful only to detect late macroscopic cartilage losses. Arthroscopy can detect earliest changes in cartilage, but it is invasive surgical procedure and not conducive for longitudinal monitoring of the disease. Although, MRI can detect gross focal defects of cartilage the conventional MRI has proven inconclusive for detecting early degenerative changes of cartilage such as chondromalacia. Recently we demonstrated, in ex vivo studies, that Tlp imaging of water in cartilage can track early biochemical changes in OA. In this proposal, we will develop and optimize this method for quantifying early degenerative changes in humans in vivo. We will first optimize this method for human applications in terms of sequence parameters, radiofrequency field inhomogeneities and time efficiency. This will be followed by the determination of accuracy and precision of Tlp relaxation mapping and dispersion on human subjects in vivo. We will then measure the age dependent variations of cartilage Tlp on healthy volunteers with varying age groups. In the fourth aim of the proposal, Tlp relaxation mapping will be performed on human subjects who have been diagnosed with early OA and correlate the Tlp results with size and location of arthroscopically scored lesions of cartilage. Finally, Tlp measurement on a group of early OA subjects will be performed in a temporal fashion, which will enable us to determine the efficacy of the method in longitudinal monitoring of the disease progression. Once accomplished, results from this project will enable one to use the relaxation rate as a quantitative, surrogate marker for early changes that occur before the onset of morphological changes in OA. A major advantage of this approach is that it does not require any additional hardware modification or administration of exogenous contrast agent. Successful completion of the proposed work, has the potential to profoundly affect our ability to study OA process and to diagnose and monitor the disease in a quantitative fashion.